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The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner
Ist Teil von
Cell stem cell, 2011-12, Vol.9 (6), p.575-587
Ort / Verlag
Cambridge, MA: Elsevier Inc
Erscheinungsjahr
2011
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases
Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified
Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that
Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the
Ink4/Arf locus.
Jhdm1b also cooperates with
Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming.
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► Vitamin C reduces H3K36me2/3 levels through the demethylases
Jhdm1a/1b ►
Jhdm1a/1b enhance somatic cell reprogramming ►
Jhdm1b and vitamin C suppress senescence and enhance cell proliferation ►
Jhdm1b cooperates with
Oct4 to activate the microRNA 302/367 cluster